The objectives of this research proposal are to demonstrate and characterize immunoregulatory defects among insulin dependent diabetics and to provide evidence that these defects may reflect a genetic predisposition to autoimmune pancreatic injury and ultimately insulin dependent diabetes (IDD) following viral infection. Virus induced alteration of cell surface antigens will be simulated by conjugation of lymphocytes with trinitrophenol. Trinitrophenol treated autologous lymphocytes will be used as generator cells and targets for cytotoxic effector cells. These experiments should determine whether insulin dependent diabetes is associated with a predisposition to autocytotoxicity. This could be due to a failure of normal suppressor mechanisms. Preliminary studies have shown impaired generation of suppressor cells after exposure of IDD lymphocytes to Concanavalin A. Utilizing cell mixing studies and screening of diabetic sera of cytotoxins we hope to characterize the defect in inducible suppressor cell generation. Demonstration of similar immunoregulatory defects among nondiabetic sibs of insulin dependent diabetics would provide evidence that a genetic diathesis to autocytotoxicity exists among these subjects.